The volatile anesthetic halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) causes liver damage in humans. It has been suggested that free radicals produced by the reduction of halothane may not only bind to cellular constituents but may also induce lipid peroxidation. Indeed, others have reported the spin trapping of lipid-derived radicals after halothane treatment in vitro and in vivo. Presently, two radical adduct species have been detected in the bile of living rats treated with halothane and PBN. The treatment of rats with hypoxia (12% oxygen) was required for radical adduct detection, consistent with a known requirement for hypoxia in experimental hepatotoxicity in phenobarbital-retreated rats. Isotopic studies conclusively demonstrated that both radical adduct species arose from the reductive debromination of halothane and not from lipid peroxidation, as others had previously reported. Free radical formation from ethanol in vivo has been described earlier. In vivo studies show that free radical formation from ethanol in a microsomal system is dependent upon contaminating trace metal and the production of superoxide anion, rather than upon enzymatic activity of cytochrome P-450, as reported in the literature. Thus, these studies call into question the significance of a microsomal pathway for free radical formation. Further work is being performed to determine the source of ethanol-derived free radicals in vivo and their role in toxicity.